Carcinoid tumour, though relatively rare, can provide the anaesthetist with a challenging task perioperatively. If you haven't read the review pages for this topic please select this module first, work through the pages and then return to answer these questions. These questions will the cover the anaesthetic implications of carcinoid tumour and syndrome, its prevalence, pathophysiology, clinical features and evidence for management during anaesthesia and the perioperative period.
Please estimate the number of cases of Carcinoid Tumour that you have seen since you qualified as a doctor.
Her current observations are BP 201/118, HR 100 sinus rhythm, SpO2 96% on room air and she is apyrexial.
On examination, she appears anxious, thin and pale, no jaundice and on auscultation of the chest you hear a systolic murmur, of which the patient was unaware. You note her BP had been steadily increasing since she was informed she was going for surgery.
Her bloods are as follows:
UEC: Na+ 134, K+ 3.7 urea 11 creatinine 134
FBC: Hb131 WCC9.9 platelet count 210
Question Knowledge Base
Postpone, this lady is not only at very high risk of an intraoperative life-threatening carcinoid crisis, the new murmur is worrying as it raises concerns of carcinoid heart disease. The patient should be further investigated and optimised before surgery (1, 2, 3). The renal impairment is not catastrophic, there is no hyperkalaemia nor is there evidence of sepsis. As it turned out, an echo showed she had a 22 by 10mm mass in her right atrium, most likely secondary to carcinoid heart disease, and moderate tricuspid regurgitation. A CT abdo/pelvis revealed extensive abdo/pelvic disease with pelvic masses, retroperitoneal lymphadenopathy, hepatic metastases and right-sided nephrosis.
Because the liver inactivates the bioactive products as they pass through, carcinoid syndrome only occurs in the presence of liver metastases or a primary tumour whose venous drainage is not via the portal vein (e.g. bronchial, ovarian). The venous drainage of the ovary occurs via the ovarian vein draining directly into the inferior vena cava bypassing the liver.
Side effects of octreotide include abdominal cramping (not diarrhoea), conduction defects, QT prolongation, bradycardia and nausea & vomiting.
Octreotide is used as treatment to counteract or minimise effects of mediator release. It does not in itself cause mediator release from the carcinoid tumour. Factors that trigger mediator release include alcohol, defaecation, exercise, tyramine rich foods (including chocolate and blue cheese), sympathetic stimulation associated with stress, emotional events and painful stimuli, general anaesthesia including laryngoscopy and intubation and hypotension, surgical and radiological interventions.
Carcinoid syndrome is characterised by intermittent episodes of flushing, diarrhoea, rhinorrhoea, lacrimation. Flushing is the clinical hallmark of carcinoid syndrome. Bronchospasm can occur in 10-20% of patients with carcinoid syndrome. Severely labile haemodynamics are usually not symptoms of carcinoid syndrome but of a carcinoid crisis.
True. There is a suggestion of increased risk associated with a well-educated background, birth in a large city and family history of carcinoid tumour in a first degree relative. The incidence rates derived from a series of 13,715 carcinoids, has been reported to be 2.47 and 2.58 per 100,000 per year in Caucasian men and women over the decade 1990 to 1999, while they were marginally higher for black men and women (4.48 and 3.98 per 100,000 population per year).
Carcinoid heart disease is characterised by pathognomonic plaque-like deposits of fibrous tissue that occur most commonly on valves and endocardium of the right side of the heart. Left sided valvular pathology occurs in less than 10% of patients with cardiac involvement and is almost always associated with a primary bronchial carcinoid or an atrial right to left shunt. Metastases (secondaries) to the heart are rare.
Most patients with carcinoid tumours are asymptomatic, their disease being diagnosed incidentally at surgery, endoscopy or autopsy. 24 hour Urinary 5-HIAA (sensitivity 73% and specificity 100%) is less sensitive but more specific than serum chromagraffin A (sensitivity 80%, specificity 95%) in diagnosing carcinoid tumour. Tumours appear as isodense, hypervascular lesions on CT.
Even patients with minimal symptomatology may experience life-threatening carcinoid crises intraoperatively as the stimulus for mediator release during surgery and anaesthesia is much higher than in everyday life. 2. Intraoperative haemodynamic instability is not always due to mediator release but may be due to fluid losses/excess bleeding, especially during resection of liver metastases, which ought to be treated with fluid resuscitation rather than octreotide. 3. Urinary 5-HIAA is a good biological marker of carcinoid tumour activity and a high value is predictive of increased likelihood of perioperative morbidity. 4. Invasive blood pressure monitoring must be in use for all cases as haemodynamic changes may occur very quickly and need a prompt response. 5. Postoperative crises do occur and surgery may only have been a debulking, therefore, ongoing control of hormone release by octreotide administration, initially IV then SC, is important.
(a). True, Morphine is associated with histamine release and may trigger further mediator release though the evidence for this is only case based.
(b). False, the use of Suxamethonium is controversial as theoretically it can potentially cause release of peptides from the liver due to depolarisation-induced fasciculations. However Veall et al. found no evidence to support this view in their review of 21 patients undergoing laparotomy for carcinoid syndrome. They noted no difference in arterial pressure changes on induction between those who received suxamethonium and those who did not.
(c). True, Noradrenaline should be avoided entirely, it can activate kallikrein in the tumour and cause synthesis and release of bradykinin resulting paradoxically in further vasodilatation and hypotension. The reverse, severe hypertension has also been seen.
(d). False, Muscle relaxation can be achieved safely with Rocuronium.
(e). False, short acting synthetic opioids such as Fentanyl, Alfentanil and Remifentanil can be used safely.
Prior to the discovery of octreotide, drugs that inhibit serotonin synthesis (methyldopa), prevent serotonin release (phenoxybenzamine) and antagonise serotonin receptors (methysergide, ketanserin, and cyproheptadine) were used with varying efficacy.
All the statements are correct except for statement (b). Octreotide is more potent than the natural hormone somatostatin at inhibiting growth hormone, glucagon and insulin.
At first any intraoperative haemodynamic instability should be assumed to be due to vasoactive mediator release. The surgeon is most likely handling the ileal tumour by now and has triggered release of vasoactive mediators. The best initial response is to administer octreotide 20-50mcg IV boluses, titrated to response. If no adequate response, one ought to consider concomitant fluid losses that should be treated with fluid replacement. However, this is unlikely to have already occurred in the above scenario half an hour into laparotomy unless the surgeons have inadvertently severed an artery/large vein. Noradrenaline should be avoided entirely as it can activate kallikrein in the tumour and cause synthesis and release of bradykinin resulting paradoxically in further vasodilatation and hypotension. Vasopressors in general should be avoided, including metaraminol, due to their unpredictable response. Phenylephrine and ephedrine have been used safely.
Thoracic epidurals do not always prevent the occurrence of perioperative carcinoid crises. They really only prevent painful stimuli from causing a carcinoid crisis. Moreover, thoracic epidurals, if not cautiously used, may provoke a carcinoid crisis by causing hypotension that may trigger mediator release.